Received September 28, 2004
Oxidative stress is considered a major contributor to etiology of both
normal senescence and severe pathologies with serious
public health implications. Mitochondria generate reactive oxygen
species (ROS) that are thought to augment intracellular oxidative
stress. Mitochondria possess at least nine known sites that are capable
of generating superoxide anion, a progenitor ROS. Mitochondria also
possess numerous ROS defense systems that are much less studied.
Studies of the last three decades shed light on many important
mechanistic details of mitochondrial ROS production, but the bigger
picture remains obscure. This review summarizes the current knowledge
about major components involved in mitochondrial ROS metabolism and
factors that regulate ROS generation and removal. An integrative,
systemic approach is applied to analysis of mitochondrial ROS
metabolism, which is now dissected into mitochondrial ROS production,
mitochondrial ROS removal, and mitochondrial ROS emission. It is
suggested that mitochondria augment intracellular oxidative stress due
primarily to failure of their ROS removal systems, whereas the role of
mitochondrial ROS emission is yet to be determined and a net increase
in mitochondrial ROS production in situ remains to be
demonstrated.
KEY WORDS: mitochondria, reactive oxygen species, superoxide,
antioxidants, oxidative stress